Abstract: Fatigue is a common, multifaceted symptom associated with the onset of functional decline in aging populations. Typically reported in absence of a specific cause, fatigue is of increasing clinical relevance because of its association with adverse health outcomes, onset of age-related disability (frailty), and premature mortality. As the geriatric population continues to grow in the US and worldwide, the ability to clinically assess and treat fatigue, as well as associated conditions (frailty) will become increasingly paramount. Fatigue has been shown to be a key clinical indicator of deterioration in quality of life for elderly populations; however, fatigue etiology is poorly understood because there is a lack of quantitative methods to assess fatigue, and its physiological and biochemical correlates are poorly understood. Clinicians primarily rely on self-reporting assessments from patients to evaluate fatigue and mobility (e.g. muscle fatigue). Such self- reporting strategies fail to capture the impact of fatigue on daily activities and quality of sleep. The resulting ambiguity limits therapeutic development and clinical interventions. The emerging concept of fatigability seeks to address this shortcoming by establishing a relationship between the experiential levels of fatigue to the intensity, duration, and/or frequency of physical activity, thereby enabling truly objective measures of fatigue. Although multiple approaches to measuring fatigability have been proposed, no standardized method or instrumentation currently exists. The present proposal addresses this unmet need with the design and development of a wearable, noninvasive, ?Tattoo-Inspired Bio-Integrated? (TIBI) platform that measures both biochemical markers from eccrine sweat together with biophysical markers for the preclinical testing and characterization of fatigability in geriatric populations. The insights from this proposed work will enable assessment of the TIBI platform in free-living fatigability measurements, enabling a new diagnostic paradigm for the onset of functional decline in aging populations.